Emergency Exception from Informed Consent (EFIC) in Planned Emergency Research

Planned Emergency Research

 

Planned emergency research involves the systematic investigation of a condition experienced by individuals “in a setting where the emergency circumstances require prompt action and generally provide insufficient time and opportunity to locate and obtain consent from” each participant or their legally authorized representative” (FDA, 2013).

 

Planned emergency research should not be confused with the FDA’s expanded access pathways for the compassionate and emergency use of an investigational drug or device in one or more patients. Expanded access of an investigational drug or device involves the treatment of a patient(s) using an investigational drug or device outside of a clinical trial.

 

On the other hand, planned emergency research involves the prospective identification and enrollment of participants into a study. Planned emergency use may or may not involve the use of a drug or device.

 

 

Exception from Informed Consent (EFIC)

 

Due to insufficient time and opportunity to locate and obtain consent, the IRB must grant either:

  • a waiver or alteration of informed consent OR
  • an exception from informed consent, also referred to as an emergency research consent waiver (DHHS, 1996).

 

Many planned emergency research protocols do not qualify for a waiver or alteration of informed consent because they fail to meet the minimal risk criterion. Research procedures for which a waiver or alteration is requested must meet the regulatory definition of minimal risk, meaning:

 

  • the “probability and magnitude of harm or discomfort [to participants] anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

 

If the IRB determines this criterion is not met, the waiver or alteration cannot be granted by the IRB. If the IRB determines the research involves greater than minimal risk, the research possibly may be conducted under an exception from informed consent if the regulatory criteria are met.

IRB Responsibilities

The IRB is responsible for:

  1. Ethical Review of the Research Protocol

  2. Review of the EFIC Plan

    Confirming the requirements for exception from informed consent are met

  3. If FDA Regulated:

    The IRB is responsible for confirming the protocol will be carried out under an investigational new drug application (IND) or investigational device exemption (IDE), as applicable, with an associated EFIC plan submitted to the FDA that aligns with 21 CFR Section 50.24.

  4. If not FDA regulated:

    The IRB is responsible for reporting to the U.S. Office of Human Research Protections that the exception from informed consent requirements are met.

Research Protocol Preparation

 

Because informed consent cannot be obtained prior to initiating research procedures, there are many additional participant protections that must be in place before the IRB can approve planned emergency research.

 

Significant preparation is required when an investigator undertakes planned emergency research under an EFIC. Research that will use an EFIC consent model undergoes a multiple-stage IRB review process where the initial approval does not include approval to commence enrollment. Therefore, EFIC reviews can take significantly longer than standard reviews. This should be taken into account while planning.

 

Most planned emergency research studies can be considered “approved to enroll participants” when all of the following has occurred:

  • The Community Consultation & Public Disclosure Plans have been reviewed and approved by the IRB;
  • The plans have been implemented in the local community;
  • The results from Community Consultation have been reviewed and approved by the IRB; and
  • As applicable, if the study is subject to FDA regulations, the FDA has approved the IND or IDE and the EFIC plan.

 

Begin by drafting your research protocol and reviewing associated guidance from the IRB and, as applicable, the FDA.

Vulnerable Population Considerations

NOTE: According to DHHS guidance (1996), an exception from informed consent is not permissible, due to special regulatory limitations, for research involving the following vulnerable populations:

  1. Fetuses

  2. Pregnant Persons

  3. Human In Vitro Fertilization

  4. Incarcerated Persons

 

However, given the emergent circumstances under which participants will be enrolled, it may not be apparent that a participant is a prisoner or pregnant at the time of enrollment. Likewise, a participant could become a prisoner or pregnant following enrollment and during the study period (including long-term follow-up periods).

 

Therefore, the protocol should be clear that known prisoners will not be enrolled and should address the plan for safely removing participants from the study who become prisoners after enrollment.

 

Investigators should also carefully consider the impact that the study intervention could have on a pregnant woman or fetus where the pregnancy is not identified at the time of enrollment. A plan for pregnancy testing prior to enrollment (if feasible and appropriate) or follow-up to ensure the safety of pregnant women and fetuses after incidental enrollment should be described in the protocol. Any study procedures performed after pregnancy is identified must meet the Subpart B criteria of 45 CFR Part 46.

 

Children may be included in EFIC protocols provided that the Subpart D criteria of 45 CFR Part 46 are met.

EFIC Protocol Preparation

 

It is very important that investigators who wish to design planned emergency research review all of the regulatory requirements for such a design. Unpreparedness may lead to the study protocol being tabled by the IRB and thus delaying the start of the project.

 

The IRB strongly recommends consulting with the IRB at the onset of planning. The IRB also recommends having a standalone EFIC protocol that outlines all of the EFIC eligibility rationale, plans, and procedures.

 

In your EFIC protocol, be prepared to provide detailed information about each of the additional human protections. These are the minimum requirements outlined in federal guidance.

 

  • EFIC Eligibility
  • A Community Consultation Plan
  • A Pre-Trial Public Disclosure Plan
    • Including a plan for participants to opt-out of the research, if appropriate
  • A Post- Trial Public Disclosure Plan
  • A Data and Safety Monitoring Plan

 

The Emergency Exception from Informed Consent (EFIC) Protocol Preparation Guide linked below outlines what should be covered to address these minimum requirements. 

EFIC Protocol Preparation Guide

Overview of EFIC Process

 

Below is an overview of the EFIC process.